We have been using AutoQC for a few years now (wow time flies!) and we have noticed that the most difficult portion of using the tool in practical 'go/no go' decisions is defining the "guide set" of runs. This is because it is very difficult to find a set of runs which have enough variation for all the metrics, without having too much variation for any of them, to properly capture the reference range. A good example would be retention time; If you perform 5 injections on 5 separate days, while running samples, you might get a good handle on most of the metrics for AutoQC. However if you are using commercial columns the retention time may be extremely tight within that window (say <15-30 seconds variability) which is too narrow to accommodate a column change or larger drifts over time, which may be somewhere in the neighborhood of +/- 1 minute. If we then start using larger sets of runs for guide sets, it is very difficult to find a set of runs over weeks or maybe even a month, which do not contain a single outlier for any of the metrics (and we in theory would not want to have outliers in the 'guide set'). Additionally, some metrics (such as mass accuracy) would make sense to have an 'absolute' cutoff window as opposed to a guide set in any case; for instance, we want all ions to have standard deviation of +/- 1.5 ppm. Allowing the user to utilize historical data to manually set a range for each metric may be more time-consuming for the user to set up, but it would perhaps lead to more accurate go/no go decisions. Another (slightly less appealing) option might be to still use the software to establish a 'guide set', but allow the user to exclude specific runs from specific individual metrics.